These studies examine the correlation of dysregulated insulin secretion and specific genetic defects in congenital hyperinsulinism. Methods include acute insulin responses (AIR) to secretogogs and long-term insulin regulation under graded hyperglycemic stimulation (GHS). AIR and GHS tests in SUR-/- patients indicate that they are blind to high as well as low glucose, perhaps contributing to the high risk of diabetes in these patients post- pancreatectomy. Patients with GLUD1 mutations (hyperinsulinism / hyperammonemia syndrome) have distinctive positive AIRs to leucine, suggesting that this disorder represents the previously described, "leucine sensitive hypoglycemia". Current work is evaluating whether AIR tests will make it possible to distinguish between infants with focal vs diffuse pancreatic lesions and infants with prolonged hyperinsulinism due to perinatal stresses.